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ID 57792
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Author
Sumi, Tomonari Research Institute for Interdisciplinary Science, Okayama University ORCID Kakenhi publons
Koga, Kenichiro Research Institute for Interdisciplinary Science, Okayama University ORCID Kakenhi
Abstract
Understanding the dominant factor in thermodynamic stability of proteins remains an open challenge. Kauzmann's hydrophobic interaction hypothesis, which considers hydrophobic interactions between nonpolar groups as the dominant factor, has been widely accepted for about sixty years and attracted many scientists. The hypothesis, however, has not been verified or disproved because it is difficult, both theoretically and experimentally, to quantify the solvent effects on the free energy change in protein folding. Here, we developed a computational method for extracting the dominant factor behind thermodynamic stability of proteins and applied it to a small, designed protein, chignolin. The resulting free energy profile quantitatively agreed with the molecular dynamics simulations. Decomposition of the free energy profile indicated that intramolecular interactions predominantly stabilized collapsed conformations, whereas solvent-induced interactions, including hydrophobic ones, destabilized them. These results obtained for chignolin were consistent with the site-directed mutagenesis and calorimetry experiments for globular proteins with hydrophobic interior cores.
Published Date
2019-3-26
Publication Title
Scientific Reports
Volume
volume9
Publisher
Nature Publishing Group
Start Page
5186
ISSN
2045-2322
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© The Author(s) 2019
File Version
Publisher
PubMed ID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1038/s41598-019-41518-1
License
https://creativecommons.org/licenses/by/4.0/
Funder Name
Japan Society for the Promotion of Science
助成番号
JP16K05657
JP26287099
JP18KK0151